AML Mutations May Influence Immune Function After Stem Cell Transplant

By David Costill
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A study published in the New England Journal of Medicine found that hematopoietic stem cell transplantation did not produce different mutations in patients with acute myeloid leukemia who relapse after transplantation.

“As consolidation therapy for acute myeloid leukemia (AML), allogeneic hematopoietic stem-cell transplantation provides a benefit in part by means of an immune-mediated graft-versus-leukemia effect,” Matthew J Christopher, MD, PhD, of the Division of Oncology in the Department of Internal Medicine at the McDonnell Genome Institute, and colleagues wrote. “We hypothesized that the immune-mediated selective pressure imposed by allogeneic transplantation may cause distinct patterns of tumor evolution in relapsed disease.”

​Stem cell transplant. Source: Getty

The researchers compared AML mutation outcomes after hematopoietic stem cell transplantation to AML mutation outcomes after treatment with chemotherapy. They paired 15 patients with relapse AML hematopoietic stem cell transplantation with 20 patients who relapsed after chemotherapy. RNA sequencing and flow cytometry were performed on a subgroup of samples for result validation.

Christopher and colleagues found that hematopoietic stem cell transplantation in patients with AML was not associated with acquiring new relapse-specific AML mutations after treatment.

However, the researchers found that AML cells that were not detected “frequently had dysregulation of a number of pathways that regulate immune function.”

The researchers posited that these findings could influence treatment strategies to combat the graft-versus-leukemia effect.

“AML relapse after transplantation was not associated with the acquisition of relapse-specific mutations in immune-related genes,” they concluded. “However, it was associated with dysregulation of pathways that may influence immune function, including down-regulation of MHC class II genes, which are involved in antigen presentation. These epigenetic changes may be reversible with appropriate therapy.”